Levetiracetam in Alzheimer's Disease: Do Epileptologists Already Have the Cure?
Levetiracetam in Alzheimer's Disease: Do Epileptologists Already Have the Cure?
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左乙拉西坦治疗阿尔茨海默病：癫痫医生已经有治疗方法了吗？
DOI：
10.1177/15357597221096020
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发表时间：
2022-07
影响因子：
3.6
通讯作者：
Sarkis, Rani A.
中科院分区：
文献类型：
--
作者：
Sarkis, Rani A.
左乙拉西坦对伴有和不伴有癫痫样活动的阿尔茨海默病患者认知功能的影响：一项随机临床试验Vossel K，Ranasinghe KG，Beagle AJ，et al. JAMA Neurol. 2021;78（11）：1345-1354. doi：10.1001/jamaneurl.2021.3310。网络过度兴奋可能导致阿尔茨海默病（AD）患者的认知功能障碍。确定抗癫痫药物左乙拉西坦改善AD患者认知功能的能力。左乙拉西坦治疗阿尔茨海默病相关网络过度兴奋（LEV-AD）研究是一项2a期随机、双盲、安慰剂对照、交叉临床试验，在加州大学旧金山分校弗朗西斯科和明尼苏达大学双子城分校进行，于2014年10月16日至2020年7月21日在34名AD成人中进行。参与者是80岁及以下的成年人，他们的简易精神状态检查评分为18分或更高，和/或临床痴呆评分低于2分。筛选包括夜间视频脑电图和1小时静息脑磁图检查。A组给予安慰剂，每日2次，共4周，随后为4周的洗脱期，然后口服左乙拉西坦125 mg，每日2次，共4周。B组采用逆序贯治疗。主要结局是左乙拉西坦治疗改善执行功能的能力（通过美国国立卫生研究院执行能力：神经行为评价和研究的措施和工具[NIH-神经行为评价和研究]综合评分测量）。次要结果是认知（通过Stroop颜色和单词测试[Stroop]干扰命名子量表和阿尔茨海默病评估量表-认知子量表测量）和残疾。探索性结果包括癫痫样活动参与者在虚拟路线学习测试中的表现以及认知和功能测试得分。在接受资格评估的54名成年人中，11人不符合研究标准，9人拒绝参与。共有34名AD成人（21名女性[61.8%];平均[SD]年龄62.3 [7.7]岁）入组并随机分配（17名参与者分配至A组，17名参与者分配至B组）。13名参与者（38.2%）被归类为具有癫痫样活动。共有28名参与者（82.4%）完成了研究，其中10名（35.7%）有癫痫样活动。总的来说，左乙拉西坦治疗没有改变NIH-EQUINER综合评分（与安慰剂相比的平均差异为0.07分; 95%CI为-0.18至0.32分; P = 0.55）或次要指标。然而，在癫痫样活动的参与者中，左乙拉西坦治疗改善了Stroop干扰命名子量表（与安慰剂相比，净改善7.4分; 95% CI，0.2 -14.7分; P = 0.046）和虚拟路线学习测试（t = 2.36; Cohen f2 = 0.11; P = 0.02）的表现。没有因不良事件而停止治疗。在这项随机临床试验中，左乙拉西坦的耐受性良好，尽管它没有改善主要结局，但在预先规定的分析中，左乙拉西坦改善了AD和癫痫样活动患者的空间记忆和执行功能任务的表现。这些探索性的研究结果需要进一步评估AD的抗癫痫方法。
Effect of Levetiracetam on Cognition in Patients With Alzheimer Disease With and Without Epileptiform Activity: A Randomized Clinical Trial Vossel K, Ranasinghe KG, Beagle AJ, et al. JAMA Neurol. 2021;78(11):1345-1354. doi:10.1001/jamaneurol.2021.3310. Network hyperexcitability may contribute to cognitive dysfunction in patients with Alzheimer disease (AD). To determine the ability of the antiseizure drug levetiracetam to improve cognition in persons with AD. The Levetiracetam for Alzheimer’s Disease–Associated Network Hyperexcitability (LEV-AD) study was a phase 2a randomized double-blinded placebo-controlled crossover clinical trial of 34 adults with AD that was conducted at the University of California, San Francisco, and the University of Minnesota, Twin Cities, between October 16, 2014, and July 21, 2020. Participants were adults 80 years and younger who had a Mini Mental State Examination score of 18 points or higher and/or a Clinical Dementia Rating score of less than 2 points. Screening included overnight video electroencephalography and a 1-hour resting magnetoencephalography examination. Group A received placebo twice daily for 4 weeks followed by a 4-week washout period, then oral levetiracetam, 125 mg, twice daily for 4 weeks. Group B received treatment using the reverse sequence. The primary outcome was the ability of levetiracetam treatment to improve executive function (measured by the National Institutes of Health Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research [NIH-EXAMINER] composite score). Secondary outcomes were cognition (measured by the Stroop Color and Word Test [Stroop] interference naming subscale and the Alzheimer’s Disease Assessment Scale—Cognitive Subscale) and disability. Exploratory outcomes included performance on a virtual route learning test and scores on cognitive and functional tests among participants with epileptiform activity. Of 54 adults assessed for eligibility, 11 did not meet study criteria, and 9 declined to participate. A total of 34 adults (21 women [61.8%]; mean [SD] age, 62.3 [7.7] years) with AD were enrolled and randomized (17 participants to group A and 17 participants to group B). Thirteen participants (38.2%) were categorized as having epileptiform activity. In total, 28 participants (82.4%) completed the study, 10 of whom (35.7%) had epileptiform activity. Overall, treatment with levetiracetam did not change NIH-EXAMINER composite scores (mean difference vs placebo, .07 points; 95% CI, −.18 to .32 points; P = .55) or secondary measures. However, among participants with epileptiform activity, levetiracetam treatment improved performance on the Stroop interference naming subscale (net improvement vs placebo, 7.4 points; 95% CI, .2–14.7 points; P = .046) and the virtual route learning test (t = 2.36; Cohen f2 = .11; P = .02). There were no treatment discontinuations because of adverse events. In this randomized clinical trial, levetiracetam was well tolerated and, although it did not improve the primary outcome, in prespecified analysis, levetiracetam improved performance on spatial memory and executive function tasks in patients with AD and epileptiform activity. These exploratory findings warrant further assessment of antiseizure approaches in AD.
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DOI：
10.1073/pnas.1121081109
发表时间：
2012-10-16
影响因子：
11.1
作者：
Sanchez, Pascal E.;Zhu, Lei;Mucke, Lennart
通讯作者：
Mucke, Lennart
影响因子：
16.2
作者：
Bakker A;Krauss GL;Albert MS;Speck CL;Jones LR;Stark CE;Yassa MA;Bassett SS;Shelton AL;Gallagher M
通讯作者：
Gallagher M
影响因子：
11.2
作者：
Vossel, Keith A.;Ranasinghe, Kamalini G.;Beagle, Alexander J.;Mizuiri, Danielle;Honma, Susanne M.;Dowling, Anne F.;Darwish, Sonja M.;Van Berlo, Victoria;Barnes, Deborah E.;Mantle, Mary;Karydas, Anna M.;Coppola, Giovanni;Roberson, Erik D.;Miller, Bruce L.;Garcia, Paul A.;Kirsch, Heidi E.;Mucke, Lennart;Nagarajan, Srikantan S.
通讯作者：
Nagarajan, Srikantan S.
DOI：
10.1038/nrn.2016.141
发表时间：
2016-12
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Palop JJ;Mucke L
通讯作者：
Mucke L
影响因子：
64.3
作者：
Liu, Kathy Y.;Schneider, Lon S.;Howard, Robert
通讯作者：
Howard, Robert